The preparation and delivery of intravenous drugs must be done using aseptic techniques and with careful attention to proper dosage. Particularly, cancer patients with depressed immune systems from treatments, have a greater susceptibility of infection. Therapeutic agents often are manufactured in lyophilized or powdered form for stability or ease in handling and shipping. The dry form of the therapeutic agent is admixed with the appropriate volume of sterile diluent to provide a uniform mixture and reconstitute the drug.
A typical procedure for reconstitution of an intravenous drug includes several steps. A drug in dry form typically is received in a vial. A syringe is used to withdraw the appropriate volume of sterile diluent from a diluent container and inject the diluent solution into the drug vial. The drug vial and diluent vial typically have rubber stoppers and the needle of the syringe is injected in and out of the stoppers.
The drug and diluent are admixed in the drug vial. Often the dry form drug is difficult to mix into solution in the diluent. Some drugs need to be reconstituted in a liquid prior to administration. Other drugs have a shorter stability period and once mixed with a liquid must be frozen to maintain efficacy for a prolonged period of time. For intravenous usage, the drugs must be in solution and placed into an intravenous delivery system. The appropriate dosage may require additional dilutions or other manipulation including adding other drugs to the mixture.
There are a variety of intravenous delivery systems. A common device is a flexible bag or vial with a fill portal and intravenous delivery tube for the patient. Intravenous infusors have been developed which have a tube with an expanding latex bladder inside the vial which has an injection port on one end of the bladder, accessible from outside the vial, to add the drug and an intravenous delivery tube on the other end of the bladder, extending outside the vial.
The multiple steps and manipulations of intravenous drug preparation and delivery equipment increase the chance for a failure in aseptic technique. The multiple transfer of a dosage increases the chance for waste of the drug or improper dosage due to potential loss during transfer.
Also, there is a risk of exposure to certain drug products such as oncolytic chemotherapeutic agents which are mutagenic or otherwise harmful to the health care worker handling the agent. In particular, when injecting a drug vial under pressure while withdrawing the syringe, there can be an aerosol effect which causes an emission of a spray from the rubber stoppered vial if the pressure in the vial is not released. The exposure of health care workers to oncolytic agents has been reported in Anderson et al., "Risk of Handling Injectable Antineoplastic Agents," Am. J. Hosp. Pharm., Vol. 39, pp. 1881-1887 (1982).
Some medications are sold premixed with various diluents. The premixing can affect the stability of some drugs and others must be frozen to maintain therapeutic efficacy. Other systems include a sealed vial which is received into a neck on a bag filled with fluid. A cap is broken off inside the bag to release the drug out of the vial. This system has several steps of preparation and requires properly sized vials and other equipment to perform the mixing.
Another system includes an amount of lyophilized or dry drug in a compartment of a container and a diluent in another compartment separated by an impervious rubber stopper. When ready for use the rubber stopper separating the diluent and the drug is dislodged and the components are mixed. The mixture must be withdrawn from the container and placed in an administration system.
In another system a one piece bag with upper and lower chambers is divided by a pinch clamp which is released to mix the two premeasured liquid components contained in the chambers. The liquids from the two chambers are manipulated to achieve mixing and fall by gravity to the lower chamber when the bag is held upright.
The apparatus and method of the present invention uses two containers, one holding a diluent and the other containing an adequate amount of the dry therapeutic agent. The containers are manufactured with the constituent components and either joined during fabrication or later. The connection joining the two containers has a flow control to selectively open and close communication between the two containers.
Typically the apparatus is used with the first container containing the diluent connected above the second container with the dry form therapeutic agent to be put into solution for intravenous administration. The connector with the flow control is opened so that diluent goes into the second container by gravity flow. After the diluent is added, the mixing occurs preferably with the flow control closed on the connector.
In one embodiment, the two containers are flexible bags that are permanently joined during manufacture with a dosage of drug in the second container and the appropriate volume of diluent in the first container. The bags are joined with a sealed tubular connector with a flow control device such as a two-way stop cock in between. In another embodiment, the two bags can be manufactured without joinder, but have a connection means which can be maintained sterile prior to using.
The method of this invention includes the fabrication of two containers, the first which holds diluent and the second that contains a dry form therapeutic agent. The two containers are joined. At the connection, the flow from the first container into the second container can be controlled. When the drug is intended to be administered, the mixing occurs. The mixture can be dispensed or administered intravenously from one of the containers. The drug is freshly reconstituted at the time of administration.
This apparatus and method is designed to provide a flexible and simple way to handle therapeutic agents. The system reduces the chance for loss of sterility, exposure to harmful agents and improper dosage. The system is also efficient for use by health care professionals since no measuring or transfer of diluent or drug is necessary in the single dosage application. In a multiple dosage system of this invention the handling and transfer are minimal.
The dual container system of the present invention is flexible because the diluent and therapeutic agent can be handled separately during the manufacturing process. If one of the components is heat labile and cannot withstand certain sterilization procedures such as autoclaving, the sterilization procedure can be different for each container and its contents prior to connection. During manufacturing, there is flexibility depending on a need for which and how much diluent or drug is chosen to be placed in the containers. This procedure can enhance the ability to fill specific orders matching the drug and the amount and type of diluent.